Description
 

Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female sex hormone.  It is one of three major endogenous estrogens, the others being estradiol and estrone.  Levels of estriol in women who are not pregnant are almost undetectable.  However, during pregnancy, estriol is synthesized in very high quantities by the placenta and is the most produced estrogen in the body by far,^[3][4] although circulating levels of estriol are similar to those of other estrogens due to a relatively high rate of metabolism and excretion.  Relative to estradiol, both estriol and estrone have far weaker activity as estrogens.

In addition to its role as a natural hormone, estriol is used as a medication, for instance in menopausal hormone therapy; for information on estriol as a medication, see the estriol (medication) article.

Biological activity

Estriol is an estrogen, specifically an agonist of the estrogen receptors ERα and ERβ.  It is a far less potent estrogen than is estradiol, and as such is a relatively weak estrogen.  According to one in vitro study, the relative binding affinity (RBA) of estriol for the human ERα and ERβ was 11.3% and 17.6% of that estradiol, respectively, and the relative transactivational capacity of estriol at the ERα and ERβ was 10.6% and 16.6% of that of estradiol, respectively.  According to another in vitro study however, the RBA of estriol for the ERα and ERβ were 14% and 21% of those of estradiol, respectively,  suggesting that unlike estradiol and estrone, estriol may have preferential affinity for ERβ.

Although estriol is an efficacious agonist of the ERs, it is reported to have mixed agonist-antagonist (partial agonist) activity at the ER; on its own, it is weakly estrogenic, but in the presence estradiol, it is antiestrogenic.  Given by subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol.  It is notable that unlike estriol, estrone can be metabolized into estradiol, and most of its potency in vivo is in fact actually due to conversion into estradiol.

In addition to acting as an agonist of the nuclear ERs, estriol also acts as an antagonist of the GPER at high concentrations, a membrane estrogen receptor where, conversely, estradiol acts as an agonist.  Estradiol increases breast cancer cell growth via activation of the GPER (in addition to the ER), and estriol has been found to inhibit estradiol-induced proliferation of triple-negative breast cancer cells through blockade of the GPER.